The subspecies of Treponema pallidum cause chronic infections, of which syphilis and yaws are the most common, that affect well over one million persons throughout the world. The diseases are characterized by periods of early and late active disease, interrupted by periods of latency lasting from weeks to decades. Although the major antigens of Treponema pallidum have been under investigation for the past five years, the mechanisms of the host's immune response to syphilis have not been well characterized in terms of individual treponemal antigens. This application proposes the continued characterization of the major protein antigens of Treponema pallidum in terms of physical- chemical nature and antigenic determinants, and an examination of the cellular and humoral mechanisms triggered by these individual antigens. The characterizations of the cellular immune response of syphilitic rabbits to individual treponemal antigens will be examined using lymphocyte proliferation and lymphokine release assays. In order to determine which antigens stimulate the production of antibodies with defined anti-treponemal function, monospecific antibodies against individual antigenic molecules will be produced; they will be characterized in terms of their ability to immobilize, neutralize, and opsonize Treponema pallidum and block treponemal attachment to eukaryotic cells. In order to determine the efficacy of immunization with isolated antigens, humoral and cellular immune responses, and the degree of resistance to challenge, will be examined in rabbits immunized with individual treponemal antigens. It is anticipated that these studies will provide a clearer definition of the important antigenic molecules of Treponema pallidum and the immune response to individual treponemal antigens; these findings may serve as the basis for the development of more specific serodiagnostic tests and, ultimately, effective immunization procedures.